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Khe Hoang-Xuan

Publications and source records attributed to Khe Hoang-Xuan.

10 recordsLinked to original sources
PubMed2006

Prognostic impact of molecular markers in a series of 220 primary glioblastomas.

BACKGROUND: In contrast to oligodendrogliomas, molecular predictors of prognosis have not been consistently found in glioblastomas. However, genetic studies show that glioblastomas consist of several genetic subtypes and raise the possibility that molecular alterations could be predictive of survival. METHODS: A search for loss of heterozygosity (LOH) on chromosome 1p, 9p, 10q, 19q, EGFR (epidermal growth factor receptor), CDK4, and MDM2 (mouse double minute) amplifications, CDKN2A (INK4A/ARF) homozygous deletions, p53 expression, was performed in a series of 220 primary glioblastomas. The molecular alterations were then correlated with each other to identify distinct molecular pathways and with clinical parameters and the course of the disease to identify prognostic markers. RESULTS: Nonrandom associations were found between EGFR amplification and LOH10q, LOH9p, and INK4A/ARF deletion, LOH1p and LOH19q, and MDM2 and CDK4 amplification, whereas mutual exclusions were found between p53 expression and EGFR amplification, LOH 9p/INK4A/ARF homozygous deletion, and MDM2 and CDK4 amplification. Age (P = 4.10(-5)) and performance status (P = .003) were the main predictors of outcome. In contrast, molecular markers were of limited impact: MDM2 amplification correlated with poor outcome on both univariate and multivariate analysis (P = .01) and EGFR amplification with good prognosis on multivariate analysis (P = .02). CONCLUSION: Despite their limited prognostic impact, the genetic markers investigated here outline distinct molecular pathways involved in glioblastoma tumorigenesis and warrant broader molecular screening.

Adolescent↗
PubMed2006

Loss of 22q chromosome is related to glioma progression and loss of 10q.

Loss of heterozygosity (LOH) of chromosome 22q has been investigated in 160 gliomas. LOH at one or more microsatellite increased with increasing grade of the tumor (P < 0.01). LOH22q was more frequent in astrocytic tumors (37%) compared to mixed or oligodendroglial tumors (21%) (P = 0.02). LOH22q was correlated to 10q loss but not to 1p or 9p loss. Taken together, these data suggest that LOH22q is an alteration associated with malignant progression of gliomas.

Brain Neoplasms↗
PubMed2006

High-dose chemotherapy followed by autologous hematopoietic stem cell transplantation for adult histiocytic disorders with central nervous system involvement.

We postulated that high-dose chemotherapy (HDC) followed by peripheral autologous hematopoietic stem cell transplantation might help to control refractory central nervous system (CNS) histiocytic disorders. Six patients with histiocytic CNS involvement were treated in this way. Two patients achieved non-active disease status, although one relapsed at 84 months. Two patients had regressive disease, one of whom progressed at 21 months. One patient had progressive disease at 14 months. One patient had extra-CNS progression but CNS regression. After a median follow-up of 22.4 months, only one of the six patients still has non-active disease. Treatment was effective on craniofacial and space-occupying brainstem lesions, and was ineffective on neurodegenerative lesions.

Adult↗
PubMed2004

Phase II study of temozolomide without radiotherapy in newly diagnosed glioblastoma multiforme in an elderly populations.

BACKGROUND: Currently, the survival of patients age > 70 years with glioblastoma multiforme (GBM) ranges from 4 months to 6 months, although radiotherapy and/or chemotherapy may prolong survival in certain subgroups. Temozolomide is an oral chemotherapeutic agent with efficacy against malignant gliomas and a favorable safety profile. This open-label, single-center, Phase II study was designed to evaluate the efficacy and safety of temozolomide as first-line chemotherapy and exclusive treatment in elderly patients with newly diagnosed GBM. METHODS: Chemotherapy-naïve patients (age > 70 years) were treated with temozolomide at a dose of 150-200 mg/m(2) per day for 5 consecutive days of a 28-day cycle until they developed disease progression. No radiation therapy was administered. The primary endpoint was median overall survival (OS); secondary endpoints included progression-free survival (PFS) and toxicity. RESULTS: Thirty-two patients (median age, 75 years; median Karnofsky performance status, 70) experienced a median OS of 6.4 months and a median PFS of 5.0 months. Of 29 patients who were assessed for response, 9 patients (31%) achieved a partial response, 12 patients (41%) maintained stable disease, and 8 patients (28%) developed progressive disease. Adverse events primarily were mild, with NCI CTC Grade 3-4 thrombocytopenia and neutropenia reported to occur in 6% and 9% of patients, respectively. No neurotoxicity was observed. Treatment delays and dose reductions occurred in 13% and 14% of cycles, respectively. CONCLUSIONS: Temozolomide represents a safe, easily administered, and effective therapeutic approach for elderly patients with newly diagnosed GBM.

Aged↗
PubMed2004

Loss of 14q chromosome in oligodendroglial and astrocytic tumors.

Loss of chromosome 14q has been investigated in 142 gliomas. Loss of heterozygosity (LOH) at one or more microsatellite has been found in 8/30 grade II (27%) and 2/21 grade III (10%) oligodendrogliomas, 3/9 grade II (33%) and 5/15 grade III (33%) oligoastrocytomas, 0/9 grade II (0%) and 1/7 grade III (14%) astrocytomas, 11/51 glioblastomas (22%). Two minimal regions were identified on 14q21.2-14q24.3 (between D14S288 and D14S74) and 14q31.3-14q32.1 (between D14S74 and D14S65). Loss of 14q was not correlated to survival, histological grading and subtype or other genetic alterations, except for 1p deletions. Taken together, these data suggest that LOH14q is an early alteration involving 20% of glioma.

Astrocytoma↗
PubMed2003

Primary brain tumours in adults.

The most frequent primary brain tumours in adults are gliomas and primary CNS lymphomas. In gliomas, molecular genetic analysis plays an increasing part in classification and treatment planning, a feature well illustrated by the chemosensitive oligodendrogliomas. Unfortunately, management of glioblastoma is still mainly palliative. Incidence of primary CNS lymphoma has increased strikingly in the past 20 years; substantial progress has been achieved in patients who are immunocompetent with the addition of methotrexate-based chemotherapy to radiotherapy, but the potential neurotoxic effects of this combination in elderly patients is worrisome.

Adult↗
PubMed2003

Oligodendrogliomas: an update on basic and clinical research.

Oligodendrogliomas have been the focus of considerable interest over the past decade, ever since they were recognized as chemosensitive tumors. They were once believed to represent less than 5% of gliomas, but by using expanded criteria, they may well represent up to one third. In fact, morphologic criteria are vague and highly subjective and the histologic diagnosis, therefore, remains highly controversial and unsatisfactory. New oligodendrocytic lineage markers, such as OLIG1/2 gene, will probably help to define the real spectrum of oligodendroglial tumors, which may include a wide variety of tumors with very different prognoses. Recently, genetic markers, and particularly loss of 1p and 19q chromosomes, have been shown to predict both prognosis and response to treatment. There is little doubt that these emerging techniques will be very helpful in clinical practice for refining both classification and therapeutic indications of oligodendroglial tumors.

Animals↗
PubMed2002

OLIG-1 and 2 gene expression and oligodendroglial tumours.

OLIG 1/2 genes encode basic helix-loop-helix transcription factors that play a critical role in motor neurone and oligodendrocyte fate specification during development. Two recent studies in which OLIG transcripts were detected by in situ hybridization have reported a high expression of the OLIG genes in oligodendrogliomas. This suggests that the detection of these lineage markers could become an adjunct to the classic morphological diagnosis of these tumours. There are problems in the diagnosis of oligodendroglioma. To date, all other known oligodendrocyte lineage markers have failed to label specifically neoplastic oligodendrocytes. Deletions on chromosome 1p and 19q are much more frequent in oligodendrogliomas than in astrocytomas but these molecular alterations are not constant. For the future, when routinely available, immunohistochemical techniques using anti-OLIG antibodies on paraffin embedded tissues will allow a systematic study of a large series of tumours so that we will know the specificity and sensitivity of this investigation in diagnosis. At another level, it is possible that expression of OLIG in neoplastic oligodendrocyte might participate in the oncogenesis of oligodendrogliomas. Initial work suggests that this is probably not the case. However further in vitro and in vivo studies analysing the functional consequence of OLIG overexpression in terms of proliferation and tumour progression are needed.

Animals↗